Dietary n-6 and n-3 PUFA alter the free oxylipin profile differently in male and female rat hearts

Abstract

Oxylipins are bioactive lipid mediators synthesised from PUFA. The most well-known oxylipins are the eicosanoids derived from arachidonic acid (ARA), and many of them influence cardiac physiology in health and disease. Oxylipins are also formed from other n-3 and n-6 PUFA such as α-linolenic acid (ALA), EPA, DHA and linoleic acid (LA), but fundamental data on the heart oxylipin profile, and the effect of diet and sex on this profile, are lacking. Therefore, weanling female and male Sprague–Dawley rats were given American Institute of Nutrition (AIN)-93G-based diets modified in oil composition to provide higher levels of ALA, EPA, DHA, LA and LA + ALA, compared with control diets. After 6 weeks, free oxylipins in rat hearts were increased primarily by their precursor PUFA, except for EPA oxylipins, which were increased not only by dietary EPA but also by dietary ALA or DHA. Dietary DHA had a greater effect than ALA or EPA on reducing ARA oxylipins. An exception to the dietary n-3 PUFA-lowering effects on ARA oxylipins was observed for several ARA-derived PG metabolites that were higher in rats given EPA diets. Higher dietary LA increased LA oxylipins, but it had no effect on ARA oxylipins. Overall, heart oxylipins were higher in female rats, but this depended on dietary treatment: the female oxylipin:male oxylipin ratio was higher in rats provided the ALA compared with the DHA diet, with other diet groups having ratios in between. In conclusion, individual PUFA and sex have unique and interactive effects on the rat heart free oxylipin profile.

Spleen Oxylipin and Polyunsaturated Fatty Acid Profiles are Altered by Dietary Source of Polyunsaturated Fatty Acid and by Sex

“…However, EPA or DHA supplementation increases the proportion of their respective oxylipins more similarly to their precursor PUFA proportions in the NL fraction. Thus, as we have observed previously (Cayer et al, ; Ferdouse, , Ferdouse, ; Leng et al, ; Leng et al, ; Mendonca et al, ), our data supports that PL content influences oxylipin production, yet the contribution of the NL pool cannot be ruled out. There is evidence that other lipid classes, such as triacylglcerol, can be sources of oxylipins (Dichlberger et al, ).…”

“…This difference cannot be explained by reduced expression or activity of desaturase enzymes in the spleen since both ALA and DHA supplementation increased PL levels of EPA and thus the difference is only seen at the level of oxylipins. The effects of n‐3 diets on spleen ARA oxylipins are similar to other tissues including serum, kidney, liver (Leng et al, ), heart (Ferdouse et al, ), and adipose (Mendonca et al, ), in that the DHA and EPA diets reduced ARA oxylipins to a greater extent than the ALA diet. Furthermore, the LNA diet had no effect on ARA oxylipins here in the spleen.…”

“…Table 1 in Ferdouse et al () shows the oil sources used to achieve the desired levels of n‐3 and n‐6 PUFA in each diet. This publication and others also describe the diet and sex effects on oxylipins in kidney, liver, adipose, brain, heart, and serum in these same rats (Cayer et al, ; Ferdouse et al, ; Ferdouse et al, ; Leng et al, ; Leng et al, ; Mendonca et al, ). Briefly, the control diet contained adequate levels of essential fatty acids and high MUFA levels, while the intervention diets contained 3 g/100 g diet more ALA, EPA, DHA, or LNA at the expense of MUFA.…”

“…The effect of diet on the spleen oxylipin profile differs in many ways from other tissues from the same animals examined by our laboratory. For example, in the serum, kidney, liver (Leng et al, ), heart (Ferdouse et al, ), and adipose tissue (Mendonca et al, ), ALA‐fed rats had higher levels of multiple EPA and (except for liver and heart) DHA oxylipins, and DHA‐fed rats had higher levels of EPA oxylipins. Oxylipins from all three pathways (COX, LOX, and CYP) were increased without apparent bias.…”

“…Also, in adipose tissue, oxylipins were often more reflective of neutral lipid (NL) than PL PUFA (Cayer et al, ). Furthermore, sex was found to interact extensively with diet in heart and in some adipose tissue depots (Ferdouse et al, ; Mendonca et al, ) but not in liver, kidney, or serum (Leng et al, ).…”